Hypothyroidism and Thyroid Medication: What Popular Explanations Leave Out

The “T4 Can’t Convert to T3” Claim: What Science Actually Says

If you’ve been treated for hypothyroidism, you’ve likely seen terms like T4, T3, and sometimes even inactive T3 mentioned online—often without clear explanation. Understanding what these hormones are, and how they work together, helps clarify why some popular claims about thyroid treatment are misleading.

What Are T4, T3, and “Inactive T3”?

The thyroid gland produces hormones that help regulate metabolism, energy, body temperature, heart rate, and brain function.

• T4 (thyroxine) is the main hormone produced by the thyroid gland. It acts largely as a storage or transport hormone.

• T3 (triiodothyronine) is the active hormone that directly affects how cells function.

• Inactive T3, often called reverse T3 (rT3), is a form of T3 that does not activate thyroid receptors and therefore does not stimulate metabolism.

Under normal conditions, the body converts T4 into active T3 inside tissues such as the liver, brain, and muscles. However, T4 can also be converted into inactive T3. This is not a mistake or a failure—it is a normal regulatory mechanism.

The body tends to produce more inactive T3 during periods of:

• Acute or chronic illness

• Severe stress

• Calorie restriction or starvation

• Inflammation

In these situations, shifting T4 toward inactive T3 helps slow metabolism temporarily as a protective response. This process does not mean the body has “lost the ability” to convert T4 properly.

Most prescription thyroid medications, such as levothyroxine, contain T4, relying on the body’s normal ability to convert it into the form—active or inactive—that best fits current physiological needs.

This context is often missing when online posts claim that people “can’t convert T4 to T3.”

How Thyroid Hormones Normally Work

Your thyroid naturally releases mostly T4 and a smaller amount of T3. The majority of active T3 is produced outside the thyroid, within tissues, using specialized enzymes. This allows each organ to fine-tune its own thyroid hormone activity.

In a detailed discussion on The Drive podcast, physician and thyroid researcher Antonio Bianco explained that because this regulation happens inside tissues, standard blood tests cannot perfectly reflect thyroid hormone activity in every organ. However, these tests—especially TSH—remain useful and reliable for most people (Attia, 2024).

Importantly, this biological complexity does not mean that most people are unable to convert T4 to active T3.

Why Levothyroxine (T4) Is Still the Standard Treatment

Levothyroxine (T4) has been the standard treatment for hypothyroidism for decades. For most patients, it restores thyroid hormone balance and improves symptoms.

Large clinical trials comparing T4 alone with combined T4 + T3 therapy have shown that adding T3 does not consistently improve energy, mood, weight, or quality of life for the majority of patients (Bianco, 2024). While some individuals report feeling better on combination therapy, these results have not been consistent or predictable across studies.

Persistent Symptoms Don’t Automatically Mean Poor Conversion

About 10–20% of people treated for hypothyroidism continue to report symptoms despite having thyroid labs in the normal range. This is real and deserves attention. However, these symptoms are not specific to thyroid hormone conversion.

Fatigue, brain fog, low mood, and weight changes can also be influenced by:

• Sleep disorders

• Iron, B12, or vitamin D deficiency

• Menopause or other hormonal shifts

• Chronic stress or depression

• Autoimmune or inflammatory conditions

When these factors are present, the body may also shift T4 toward inactive T3 as part of a broader stress response. This does not indicate a permanent or pathological inability to produce active T3 (Azizi et al., 2025) t4t3.

Genetics and Combination Therapy: What’s Still Unclear

Researchers have explored whether certain genetic variations affect how thyroid hormones are activated within tissues. While this research is ongoing, no clinical test can currently identify who will reliably benefit from T3 supplementation, and findings so far have been inconsistent (Bianco, 2024).

New trials using slow-release T3 are underway, but even these studies acknowledge that previous research has not shown clear or consistent benefit compared with T4 alone (Azizi et al., 2025) t4t3.

What Thyroid Experts Recommend

Professional organizations such as the American Thyroid Association continue to recommend T4 monotherapy as first-line treatment. They note that combination therapy may be considered in select cases, but only after other causes of symptoms are evaluated and with careful monitoring due to potential risks such as heart rhythm problems and bone loss (American Thyroid Association, 2025).

Why This Claim Persists Online

The idea that “your body can’t convert T4” offers a simple explanation for ongoing symptoms. But simple explanations are not always accurate. The thyroid system is adaptive and interconnected with stress, illness, and overall health.

Bottom Line

The claim that most people cannot convert T4 to active T3 is not supported by current evidence. T4 can convert to both active and inactive T3 as part of normal regulation. Persistent symptoms deserve a whole-person evaluation, not automatic assumptions about thyroid hormone failure.

References (APA 7th Edition)

American Thyroid Association. (2025). Combination therapy with T4 and T3.https://www.thyroid.org/patient-thyroid-information/ct-for-patients/february-2025/vol-18-issue-2-p-5-6/

Attia, P. (2024). Antonio Bianco, MD, PhD: Thyroid hormone physiology, T4-to-T3 conversion, and clinical implications [Podcast episode]. The Drive.https://peterattiamd.com/antoniobianco/

Azizi, F., Amouzegar, A., Abdi, H., et al. (2025). Treatment of hypothyroidism with levothyroxine plus slow-release liothyronine: Study protocol for a randomized controlled trial. Trials, 26, 228. https://doi.org/10.1186/s13063-025-08940-5 t4t3

Bianco, A. C. (2024). Thyroid hormone replacement: Current status and future directions. European Thyroid Journal, 14(2).https://etj.bioscientifica.com/view/journals/etj/14/2/ETJ-24-0275.xml

McAninch, E. A., & Bianco, A. C. (2023). The history and future of treatment of hypothyroidism. Journal of Clinical Endocrinology & Metabolism, 108(2), 1–14.https://pmc.ncbi.nlm.nih.gov/articles/PMC12370163/